Optically active cyclohexenone derivatives are useful intermediates or building-blocks for the synthesis of various more complex compounds, such as steroids or macrocyclic ketones.
Despite this fact, to the best of our knowledge, the prior art reports only one process to carry out the cyclisation of an achiral di-ketone, in the presence of a chiral promoter, into an optically active cyclohexenone derivative (see C. Agami et al. in Bulletin de la Société Chimique de France, 1987, 358).
However said method is very specific in both the nature of the chiral promoter and in the substrate used, and therefore suffers from the drawback of being of very little versatility.
Indeed, there is disclosed only one possible chiral promoter of the cyclisation, i.e. the amino acid (S)-proline, and only a specific type of di-ketone, i.e. a 4-alkyl-2,6-heptanedione.
Moreover, the prior art does not provide any suggestion or information concerning the possibility to carry out said process with other promoters or with other substrates. Concerning the substrate, it is also useful to point out that said 4-alkyl-2,6-heptanediones are known to be more easily activated to perform aldol reactions than, for instance, a macrocyclic 1,5-di-ketone. In fact we have noticed that by applying the prior art experimental conditions to a macrocyclic 1,5-di-ketone the corresponding optically active cyclohexenone is not obtained.
Therefore, the prior art does not solve the problem of providing a process for the preparation of an optically active cyclohexenone starting from an achiral di-ketone and which is of a more broad scope in the nature of the starting material and/or in the nature of the chiral compound used to promote the aldol reaction, i.e. the cyclisation, allowing thus a greater versatility. Moreover, in particular, the prior art does not provide a solution to the problem of providing a process for the preparation of an optically active cyclohexenone derivative starting from an achiral macrocyclic di-ketone.